La protéïne Z (rôle dans l'insuffisance vasculo-placentaire et relations phénotype-génotype dans deux études cas-témoins en Haute-Normandie)

La protéine Z est une protéine vitamine K-dépendante qui agit comme inhibiteur de la coagulation en inactivant le facteur X activé. Nous avons évalué le rôle de la concentration plasmatique de PZ et des polymorphismes a-13g, g79a et g-103a du gène de la PZ dans la prééclampsie et l'hypotrophie foetale. Les analyses ont été effectuées sur des prélèvements du post-partum. Une PCR suivie d'une restriction enzymatique a été mise au point au laboratoire pour la recherche du polymorphisme g-103a du gène de la PZ. Les concentrations moyennes en protéine Z ne sont pas différentes entre les femmes ayant présenté une prééclampsie sévère ou ayant mis au monde un enfant hypotrophe sévère et les femmes avec grossesses normales. En revanche, les femmes témoins de l'étude ont plus souvent des valeurs élevées de PZ. Les déficits en PZ semblent plus fréquents chez les sujets ayant des anticorps antiphospholipides mais les résultats ne sont pas statistiquement significatifs. L'étude des polymorphismes génétiques de la PZ ne met pas en évidence de lien direct entre ceux-ci et la survenue d'insuffisance vasculo-placentaire. En revanche, il apparaît que les polymorphismes g79a et g-103a sont des déterminants de la concentration en PZ. L'étude habituelle à la recherche de thrombophilies constitutionnelles et acquises ne retrouve pas nettement de lien entre l'existence d'une thrombophilie biologique donnée et la survenue d'hypotrophie sévère ou de prééclampsie.ROUEN-BU Médecine-Pharmacie (765402102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Management of patients with inherited bleeding disorders in oral surgery: A 13-year experience

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Imaging of Oxford/AstraZeneca® COVID-19 vaccine-induced immune thrombotic thrombocytopenia

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Abnormal bleeding phenotype for mild haemophilia B patients with the p.Ile112Thr variation on the gene for factor IX

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Role of M2-like macrophage recruitment during angiogenic growth factor therapy

International audienceTherapeutic angiogenesis has yet to fulfill its promise for the clinical treatment of ischemic diseases. Given the impact of macrophages during pathophysiological angiogenesis, we asked whether macrophages may similarly modulate vascular responses to targeted angiogenic therapies. Mouse matrigel plug assay and rat myocardial infarction (MI) model were used to assess angiogenic therapy with either VEGF-A or FGF-2 with HGF (F+H) delivered locally via albumin-alginate microcapsules. The infiltration of classical M1-type and alternative M2-like macrophages was assessed. Clodronate was used to prevent macrophage recruitment, and the VEGFR2 blocking antibody, DC101, to prevent VEGF-A signaling. At 3 weeks after matrigel implantation, the combination therapy (F+H) led to increased total, and specifically M2-like, macrophage infiltration versus control and VEGF-A plugs, correlating with the angiogenic response. In contrast, VEGF-A preferential recruited M1-type macrophages. In agreement with a direct role of M2-like macrophages in F+H-induced vessel growth, clodronate radically decreased angiogenesis. Further, DC101 reduced F+H-induced angiogenesis, without altering macrophage infiltration, revealing macrophage-derived VEGF-A as a crucial determinant of tissue responsiveness. Similarly, increased cardiac M2-like macrophage infiltration was found following F+H therapy post-MI, with strong correlation between macrophage levels and angiogenic and arteriogenic responses. In conclusion, M2-like macrophages play a decisive role, linked to VEGF-A production, in regulation of tissue responsiveness to angiogenic therapies including the combination of F+H. Our data suggest that future attempts at therapeutic revascularization in ischemic patients might benefit from coupling targeted growth factor delivery with either direct or indirect approaches to recruit pro-angiogenic macrophages in order to maximize therapeutic angiogenic/arteriogenic responses

Obstetrical complications in hereditary fibrinogen disorders: the Fibrinogest Study.

BACKGROUND Women with hereditary fibrinogen disorders (HFDs) seem to be at increased risk of adverse obstetrical outcomes, but epidemiologic data are limited Patients/methods: We conducted a retrospective and prospective international study to determine the prevalence of pregnancy complications, the modalities and management of delivery, and the postpartum events. RESULTS A total of 425 pregnancies were investigated from 159 women (49 hypofibrinogenemia, 95 dysfibrinogenemia, 15 hypodysfibrinogenemia). Overall, only 55 (12.9%) pregnancies resulted in an early miscarriage, 3 (0.7%) in a late miscarriage and 4 (0.9%) in an intrauterine fetal death. Prevalence of live birth was similar among the types of HFD (p=0.31). Obstetrical complications were observed in 54 (17.3%) of live birth pregnancies, including vaginal bleeding (14, 4.4%), retroplacental hematoma (13, 4.1%), and thrombosis (4, 1.3%). Most 56deliveries were spontaneous (218, 74.1%) with a vaginal non-instrumental delivery (195, 63.3%). A neuraxial anesthesia was performed in 116 (40.4%) pregnancies, while 71 (16.6%) and 129 (44.9%) were under general or no anesthesia, respectively. A fibrinogen infusion was administered in 28 (8.9%) deliveries. Postpartum hemorrhages were observed in 62 (19.9%) of pregnancies. Postpartum venous thrombotic events occurred in 5 (1.6%) pregnancies. Women with hypofibrinogenemia were more at risk of bleeding during the pregnancy (p=0.04). CONCLUSIONS Compared to European epidemiologic data, we did not observe a greater frequency of miscarriage while retroplacental hematoma, postpartum hemorrhage and thrombosis were more frequent. Delivery was often performed without locoregional anesthesia. Our findings highlight the urgent need for guidance on management of pregnancy in HFDs

Age at diagnosis is delayed in women/girls with haemophilia compared to men/boys: a FranceCoag report

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